Excitation Contraction Coupling Flashcards
What is excitation contraction coupling?
Linkage between excitation of muscle fibre membrane and onset of contraction
What is action potential like in skeletal muscle?
Very fast - 10msec
Tension response vs Action potential in skeletal muscle:
Latent period between both
Contraction of muscle doesn’t overlap with AP
Where does latent period take place in skeletal muscle?
At peak of AP and start of contraction
What happens during latent period?
Effect of changed membrane potential
Diffusion of signalling substance from extracellular space
What effect does change in membrane potential do in latent period of skeletal muscle?
Electrical field change is limited to immediate vicinity (surrounding) of plasma membrane
Why is the diffusion of signalling substance from extracellular space highly unlikely to cause latent period in skeletal muscle?
Time for diffusion much longer than latent period
What does T-system enable?
Delivery of action potential deep into muscle fibre
Where is calcium stored?
Sarcoplasmic reticulum
What happens when action potential arrives at axon terminal in neuromuscular junction?
Acetylcholine diffuses across synaptic cleft and binds to nicotinic receptors
What are nicotinic receptors like?
Ligand-gated channels
2 molecules of ACh bind to each receptor
What happens when acetylcholine binds to nicotinic receptors?
They open and Na+ floods in (outweighs K+ moving out)
Cell depolarises
What happens after depolarisation of motor end plate?
AP propagates along surface of muscle fibre - sarcolemma
AP propagates down T-tubule membrane
What happens after action potential propagates down T-tubule?
Conformational change of DHP receptor
What happens when DHP receptor changes shape?
Foot processes pull open RYR receptor (calcium release channel)
What happens after RYR channel opens?
Calcium ions diffuse out of sarcoplasmic reticulum and flood into cytosol (down conc. gradient)
What helps calcium release from sarcoplasmic reticulum?
Calcium-binding protein called calsequestrin
What happens in latent period in skeletal muscle in regards to calcium?
There is an increase in intracellular calcium concentration
This causes muscle contraction
How is calcium recycled in skeletal muscle?
Sarcoplasmic reticulum / terminal cisternae
Cytoplasm
What are the two junctional foot proteins?
DHPR
RYR
What does DHPR stand for?
Dihydropyridine receptor protein
What type of receptor is DHPR?
L-type voltage-gated calcium channel
Where is DHPR receptor found?
T-tubule membrane
What does RYR stand for?
Ryanodine receptor protein
What type of receptor is RYR?
Calcium release channel into sarcoplasmic reticulum
What happens after calcium enters cytoplasm?
Binds to troponin C
Allows strong actin-myosin binding
What concentration does cytoplasmic calcium increase to?
10-7 M to 10-5 M
What’s the key event resulting in interaction of actin and myosin filaments?
The increase in intracellular calcium concentration
Example of dihydropyridine:
Nifedipine
What muscle does Nifedipine address?
Smooth muscle
What is nifedipine used to treat in smooth muscle?
Hypertension
Migraine
Atherosclerosis
What is What is Nifedipine?
Voltage-gated calcium channel blocking drug
Example of ryanodine:
Dantrolene
What does Dantrolene do?
Spasmolytic drug acting as skeletal muscle relaxant
Acts of ryanodine receptor
What area in muscle does dantrolene address?
Sarcoplasmic reticulum
What is dantrolene used to treat?
Muscle spasm
Malignant hyperthermia
What’s needed in order for relaxation of skeletal muscle?
Repolarisation
Removal of calcium bac to resting levels
What helps to return calcium back to resting levels?
Calcium ATPase (SERCA)
What does SERCA stand for?
Sarcoplasmic endo plastic reticulum calcium ATPase
What does SERCA do?
Forces calcium against concentration gradient
What type of process is SERCA uptake?
Active process - need energy from hydrolysis of ATP
What activates the SERCA pump in sarcoplasmic reticulum membrane?
Increase in intracellular calcium concentration
How much calcium does SERCA actively transport?
2 calcium ions per molecule of ATP hydrolysed
What does calcium concentration in cytoplasm decrease to after removed via SERCA?
Back to 10-7 M (resting levels)
What is the role of calsequestrin?
Stores calcium at high concentrations in terminal cisternae
What does the storing of calcium in calsequestrin result in?
Concentration gradient from sarcoplasmic reticulum to cytoplasm
How many calcium ions bind to calsequestrin?
23 calcium ions per molecule
Why don’t muscle cells in heart need an action potential to drive contraction?
Pacemaker cells - set electrical rhythm
WHat are pacemaker cells?
Specialised muscle cells
What is the resting potential like in pacemaker cells?
Unstable
WHat do pacemaker cells undergo?
Automatic rhythmical depolarisation
What is depolarisation of pacemaker potentials like?
They always depolarise to threshold
Fast
Graph of action potential in cardiac muscle:
Fast initial depolarisation
Partial repolarisation and then plateau due to influx of calcium
Duration of AP in cardiac muscle compared to in skeletal muscle:
Much longer - 350 ms
How is change in tension different in cardiac muscle to skeletal muscle?
There is a change in tension during action potential - an overlap
Where does 25% of required calcium for contraction go?
Enters through L-type calcium channels (DHPR) in T-tubule membrane
What happens when 25% of calcium enters DHPR receptors in cardiac muscle?
Binds to RYR receptors + trigger calcium from stores
Calcium released via RYR channels in sarcoplasmic reticulum
How is relationship between DHR and RYR different in cardiac muscle to skeletal muscle?
No mechanical coupling
It’s called calcium-induced calcium release
Describe Calcium-indicted Calcium release:
25% Calcium enters DHPR channel
Calcium binds to RYR receptor
RYR receptor opens and 75% calcium released from sarcoplasmic reticulum
What does relaxation of cardiac muscle require?
Decrease in cytoplasmic calcium concentration to 10-7 M
What happens when cytoplasmic calcium concentration decreases?
Calcium ATPase in sarcoplasmic reticulum is activated
What also helps remove calcium from cytoplasm?
Sodium:Calcium exchange in sarcolemma membrane
Requires sodium ATPase
